佐剂
生发中心
免疫系统
生物
接种疫苗
细胞因子
B细胞
脂质A
细胞
病毒学
抗体
免疫学
脂多糖
生物化学
作者
Mohamad‐Gabriel Alameh,István Tombácz,Emily Bettini,Katlyn Lederer,Sonia Ndeupen,Chutamath Sittplangkoon,Joel R. Wilmore,Brian T. Gaudette,Ousamah Younoss Soliman,Matthew Pine,Philip Hicks,Tomaz B. Manzoni,James J. Knox,John L. Johnson,Dorottya Laczkó,Hiromi Muramatsu,Benjamin Davis,Wenzhao Meng,Aaron M. Rosenfeld,Shirin Strohmeier
出处
期刊:Immunity
[Cell Press]
日期:2021-11-04
卷期号:54 (12): 2877-2892.e7
被引量:654
标识
DOI:10.1016/j.immuni.2021.11.001
摘要
Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.
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